Session 10 - Drugs Rate and Rhythm

Question 1

What is the cardiac resting membrane potential?

Answer 1

-90mV

Question 2

What sets the resting membrane potential for cardiac cells?

Answer 2

The relative permeability of the cardiac myocyte to K+

Question 3

What is the equilibrium potential of K+?

Answer 3

-80mV

Question 4

Outline a contraction of a ventricular myocyte?

Answer 4

o In diastole, the resting membrane potential of cardiac cells is close to the equilibrium potential of K+ (4).
o Initial depolarisation due to spread of electrical activity from pacemaker cells. Once threshold has been reached, fast voltage gated sodium channels are opened, causing depolarisation towards Na+’s equilibrium potential (0).
o Following the rapid depolarisation, a brief repolarisation caused by the outward flow of K+ returns the membrane potential to ~0. (1)
o Na+ channels deactivate, but the depolarisation causes the opening of voltage gated Ca2+ channels, which take longer to activate, keeping the membrane depolarised (2).
o Influx of Ca2+ causes the release of further Ca2+ from cellular stores, causing contraction (See M&R Session 5).
o After ~250ms, Ca2+ channels close.
o Efflux of K+ returns membrane potential to resting (3).

Question 5

Give the classification of anti-arythmic drugs

Answer 5

Class 1 - Na+ blockes
Class 2 - B blocekrs
Class 3 - K+ channel blockers
Class 4 - Ca2+ channel blockers

Question 6

Give three types of Na+ channel blockers

Answer 6

1a) Quinidine
1b) Lidocaine
1c) Felcainide

Question 7

Give a type of beta blocker

Answer 7

Atenolol
Bisoprolol
Metoprolol

Question 8

Give a widely used K+ channel blocker

Answer 8

Amiodarone

Question 9

Give a Ca2+ channel blocker

Answer 9

Verapamil

Question 10

What are the effects of Flecainide and Lidocaine?

Answer 10

Decrease conduction velocity
Increase depolarisation threshold
Decrease automacity

Question 11

What is the route of administration of flecainide?

Answer 11

Oral and intravenous

Question 12

What are the indications for flecinaide?

Answer 12

Supraventricular tachyarrythmias (atrial arrhythmia)

Question 13

Give two contraindications for Flecainide?

Answer 13

Heart failure, History of MI

Question 14

What is the mechanism of action for Flecainide?

Answer 14

Blocks fast, inward Na+ ion channel (Phase 0)

Question 15

Give three adverse reactions of flecainide

Answer 15

 Dizziness, visual disturbances, arrhythmias

Question 16

What are the drug-drug interactions for Flecainide?

Answer 16

 Metabolised by CYP2D6 and eliminated renally. Inducers/inhibitors

Question 17

How is lidocaine adminstered?

Answer 17

Intravenously

Question 18

What are the indications for lidocaine?

Answer 18

Ventricular arrhythmias following MIO

Question 19

What are the contraindications for Lidocaine (2)

Answer 19

AV block

Heart failure

Question 20

Give three adverse drug reactions for lidocaine

Answer 20

Hypotension, bradycardia
Nystagmus
Seizures

Question 21

What do beta blockers act on?

Answer 21

B1 receptors in the heart

Question 22

What is the action of B blockers

Answer 22

Block sympathetic action
Decrease slop of pacemaker potential in SAN
Decrease chronotrophy
Inhibits adenyl cyclase, decrease inotrophy

Question 23

What do B blockers do to ventricular action potential?

Answer 23

Shifts it to the right

Question 24

What are the indications for B blockers? (4)

Answer 24

 Angina
 Post myocardial infarction
 Hypertension
 Arrhythmias

Question 25

What are the two main contraindications for beta blockers?

Answer 25

Asthma | General decreased heart function

Question 26

What is the mechanism of action for beta blockers?

Answer 26

 Antagonise β-adrenoreceptors. β1-receptors are found in the heart, when they are activated they cause increased Chronotropy and Inotropy.  Inhibits renin release

Question 27

Give some adverse drug reactions for beta blockers

Answer 27

 Bronchospasm, fatigue and insomnia, dizziness, cold extremities, hypotension, bradycardia and decreased glucose tolerance in diabetic patients – Don’t feel adrenaline from hypoglycaemia due to B blockers, dangerous

Question 28

Give two drug-drug interactions of Beta blockers

Answer 28

 Prevents Salbutamol working (β2-adrenoagonist) |  Verapamil – Both have –‘ve inotropic action

Question 29

What do K+ channel blockers do?

Answer 29

Prolong the absolute refractory period by increase AP duration Also suppress re-entry circuits by closing excitable gap

Question 30

Why are they not generally used?

Answer 30

Torsades de pointes

Question 31

Give an example of a potassium channel blocker

Answer 31

Amiodarone

Question 32

What is the route of administration of potassium channel blockers?

Answer 32

Oral or intravenous

Question 33

What are the indications for potassium channel blockers

Answer 33

Ventricular and supraventricular arrythmia

Question 34

What are some drug-drug interactions of amiodarone?

Answer 34

Inhibits CYP3A4, CYP2C9 and P-glycoprotein |  Dose reductions of Warfarin, Digoxin, Flecainide needed

Question 35

What do Ca2+ blockers do?

Answer 35

Increased refractory period | Decreased Chronotrophy and Inotropy

Question 36

Give two examples of Calcium channel blockers

Answer 36

Verapamil | Diltiazem

Question 37

Give a route of admin for calcium

Answer 37

Oral

Question 38

Give three indications for Ca2+ blockers

Answer 38

Supraventriuclar arrhythmias | Prophylaxis and treatment of angina nad hypertension

Question 39

Give three contraindications for Calcium channel blockers

Answer 39

Heart failure Bradycardia AV node block

Question 40

Give four adverse reactions to calcium channel blockers?

Answer 40

Hypotension Bradycardia Heart failure Heart block

Question 41

What is used to treat torsades de pointes?

Answer 41

Digoxin | Adenosine

Question 42

What does adenosine do?

Answer 42

Blocks AV node

Question 43

What are the two main effects of adenosine?

Answer 43

Decrease automacity | Increased AVN refractory period

Question 44

What are two main indications for digoxin?

Answer 44

Supraventricular arrhythmias, Heart Failure

Question 45

Give two contraindications for digoxin

Answer 45

Heart block | Hypokalaemia

Question 46

Outline the mech of action of digoxin

Answer 46

``` o Inhibits Na/K-ATPase o Direct Cardiac Effects   Inotrope – Used in heart failure, no mortality benefit o CNS Effects   Sympathetic outflow   Parasympathetic outflow  Sensitises baroreceptor reflex o Combined Effects   Automaticity of SAN and AVN   AVN refractory period   Conduction velocity of AVN ```

Question 47

What are three adverse drug reactions to digoxin?

Answer 47

o Narrow therapeutic index o Toxicity enhanced with hypokalaemia o Cardiac toxicity – bradycardia, AVN block, atrial tachycardia

Question 48

Give some drugs which increase digoxin levels

Answer 48

Popafenone, Quinidine, Amiodarone, Verapamil, Spironolactone, Cylosporine

Question 49

Give some drugs which decrease digoxin levels

Answer 49

Erythromycin, Tetracycline (gut bacteria metabolise digoxin)

Question 50

Why do you split loading dose of digoxin in two?

Answer 50

To minimise toxicity risk

Question 51

How much of digoxin is protein bound

Answer 51

20-30%

Question 52

What is digoxin clearance proportional to?

Answer 52

GFR

Question 53

Give three examples of ACE inhibitors

Answer 53

 Ramipril  Lisinopril  Captopril

Question 54

Give three indications for ACE inhibitors

Answer 54

 Hypertension  Heart failure  Renal dysfunction

Question 55

Give three contraindications for ACE inhibitors

Answer 55

Pregnancy Renovascular Aortic stenosis

Question 56

Outline mech of action of ACE inhibitors

Answer 56

 ACE inhibitors cause inhibition of Angiotensin Converting Enzyme, consequently reducing Angiotensin II and Aldosterone levels. This causes vasodilation and consequent reduction in peripheral resistance and reduced sodium retention.  Reduce breakdown of the vasodilator Bradykinin

Question 57

Give five adverse reactions of ACE inhibitors

Answer 57

 Characteristic dry cough  Angio-oedema (rare, but more common in black population)  Renal Failure  Hyperkalaemia  Hypotension, dizziness and headache, diarrhoea and muscle cramps

Question 58

Give two angiotensin blockers

Answer 58

Losartan | Valsartan

Question 59

What is an indication for angiotensin blocker?

Answer 59

Hypertension

Question 60

Give four contraindications

Answer 60

 Pregnancy, breastfeeding |  Caution in renal artery stenosis and aortic stenosis

Question 61

What is the mech of action of angiotensin blocker?

Answer 61

 Bind to and antagonise the receptor for Angiotensin II – Angiotensin 1 Receptor (AT1 R).  Inhibits vasoconstriction and aldosterone stimulation by angiotensin II.

Question 62

Give two adverse drug reactions to angiotensin receptor blockers

Answer 62

 Renal failure |  Hyperkalaemia